Implants comprising biologically derived scaffolds have become important options for tissue/organ repair and regeneration in the treatment of various different diseases and conditions. A continuing major hurdle is the need for a functional blood supply for the implanted scaffold.
Patients short bowel syndrome (SBS) lack more than half of their small intestine, which may be caused by a number of disorders and typically results in surgical resection. Suitable implants would be useful in the treatment of SBS. Bowel diseases, such as Crohn's disease in adults and necrotising enterocolitis in infants, are diseases which can lead to short bowel syndrome (SBS) and consequent nutrient absorptive failure requiring a bowel transplant. This is a significant clinical issue resulting in poor quality of life, shortened life expectancy and reliance on expensive chronic care regimes for survival. It is estimated that £700 million per annum is spent on parenteral nutrition alone (excluding nursing and other care) for SBS in the EU and US.
Previous studies have used both synthetic and biological scaffolds to produce short segments of neo-intestinal tissue. For example, de-cellularised porcine small intestine sub-mucosa (SIS), a collagen based acellular matrix used for the regeneration or augmentation of diseased or non-functional biological systems, has been successfully employed to regenerate neo-intestine in small animal models. However, SIS does not retain the original vascular supply to the tissue, resulting in limited perfusion. Additionally, SIS has relatively poor mechanical and regenerative properties.
A critical hurdle in the ability to create thick complex or multilayered tissue is the requirement of a suitable vascular supply which can be the limiting factor governing the size of tissue construct. With this in place, the translation of small-scale scaffold implantation to larger grafts of real clinical relevance becomes more feasible. A pre-existing or rapidly developing vascular supply to an implanted scaffold has to be able to provide all the necessary oxygen, nutrients and growth factor(s) to ensure survival. Diffusion distances of 100 μm-200 μm limit the survival of cells from the nearest capillary and since blood vessels can take days to develop, the lack of available oxygen can potentially predispose the implant to ischemia.
Vascularisation methods have tended to focus on the synthesis of de-novo blood vessels rather than the utilization of existing vasculature attached to the biological scaffold. Since the growth of host vessels into an implanted graft can take a few weeks to occur, the grafts are often threatened by ischemia and necrosis.
Recently, a group in Germany has developed a method to obtain a biological scaffold with a feeding artery and vein as an integral part of the scaffold. The vasculature can be directly anastomosed to the host's blood supply and presents the possibility of either re-endothelisation when attached to the host or in vitro prior to implantation (Linke et al. (2007) Tissue Engineering 13(11); 2699-2707: Mertsching et al. (2009) Transplantation 88(2): 203-210; Schanz et al. (2010) Journal of Biotechnology 148(1): 56-63).